This new NIDDK P30 proposal seeks to establish a Center of Excellence in Hematology at the joint campuses of the University of Pennsylvania (UPENN) and the Children's Hospital of Philadelphia (CHOP) We believe that research and education in the field of benign hematology has achieved a critical mass a UPENN/CHOP. The 13 Investigators of this proposal are well funded by the NIH and published and have multiple co-authored papers and grants. Recent investigator driven enhancements in our research and clinical infrastructures include establishing: a) a Human Embryonic Stem Cell Center (2008);b) an overarching Blood Center focused on enhancing "bench-to-bedside" research in benign hematology (2009);and c) have recruited two new highly regarded investigators to establish a Comprehensive Adult and Pediatric Bone Marrow Failure Program to coordinate patient care as well as basic and translational research. Our educational efforts are supported by two major NIH training grants: An NIDDK benign hematopoiesis T32 and a NHLBI K12 award on benign hematology. As the number of UPENN/CHOP hematology investigators, research projects, clinical programs and trainees expand, it becomes increasingly important to focus our efforts into a cohesive, synergistic whole. To address this need, the current application seeks support to establish and maintain a multi-investigator, collaborative program on benign human hematopoiesis and associated diseases. Scientific efforts will involve three intertwined foci: 1) advancing our understanding of normal hematopoiesis and of BMF syndromes, 2) using such knowledge to develop novel therapeutic approaches for the hemoglobinopathies and BMF syndromes, as well as 3) using the knowledge gained under (1) to develop novel cellular-based therapeutics for the treatment of hematologic disorders. We believe that this propitious P30 RFA offers the opportunity to exploit and enhance our current strengths in benign hematology. Accordingly, we seek to develop an organized hematopoiesis program that will provide centralized state-of-the-art core facility technical support, offer pilot programs to attract young investigators and organize educational events. We anticipate that 5 years of such support will enhance our productivity as evidenced by important publications in the area of benign hematopoiesis, more synergistic research efforts, growth in the number of faculty and fellows focused on relevant areas and a further increase in our NIH-based funding, particularly multi-investigator grants. TABLE OF CONTENTS OVERALL DESCRIPTION 2 OVERALL CENTER CRITIQUE 3 CENTER DIRECTOR 5 OVERALL COMMITTEE BUDGET RECOMMENDATIONS 6 OVERALL ACTION 6 SUPPORT TO BE NEGOTIATED 6 RESEARCH BASE... 6 ADMINISTRATIVE CORE: Mortimer Poncz, MD, Mitchell J. Weiss, M.D., Ph.D ... 9 CORE B: HUMAN STEM CELL: Mitchell J. Weiss, M.D., PhD ... 10 CORE C: GENOMICS AND HIGH THROUGHPUT SCREENING: Scott L. Diamond, Ph.D ... 14 CORE D: XENOTRANSPLANTATION MOUSE: Martin Carroll, M.D ... 16 CORE E: MOLECULAR GENE DELIVERY/MODIFICATION CORE: Carl June, M.D ... 18 PILOT AND FEASIBILITY (P&F) PROGRAM: Poncz, MD, Mitchell J. Weiss, M.D., Ph.D. 20 PUBLIC HEALTH RELEVANCE: This proposal is to support on-going efforts in our group in understanding how the bone marrow makes blood and use this knowledge to treat a number of blood diseases as well as use this same knowledge to develop new strategies for delivering care for a wide number of diseases (cellular therapeutics). The proposal is not only to gain additional support for key research cores in the area of making blood, but also to use this to bring the various research efforts on campus into a cohesive whole.